Hydrogen sulfide attenuates lipopolysaccharide‐induced inflammation by inhibition of p38 mitogen‐activated protein kinase in microglia

Abstract

The present study attempts to investigate the effect of H 2 S on lipopolysaccharide (LPS)-induced inflammation in both primary cultured microglia and immortalized murine BV-2 microglial cells. We found that exogenous application of sodium hydrosulfide (NaHS) (a H 2 S donor, 10-300 lmol/L) attenuated LPS-stimulated nitric oxide (NO) in a concentrationdependent manner. Stimulating endogenous H 2 S production decreased LPS-stimulated NO production, whereas lowering endogenous H 2 S level increased basal NO production. Western blot analysis showed that both exogenous and endogenous H 2 S significantly attenuated the stimulatory effect of LPS on inducible nitric oxide synthase expression, which is mimicked by SB 203580, a specific p38 mitogenactivated protein kinase (MAPK) inhibitor. Exogenously applied NaHS significantly attenuated LPS-induced p38 MAPK phosphorylation in BV-2 microglial cells. Moreover, both NaHS (300 lmol/L) and SB 203580 (1 lmol/L) significantly attenuated LPS-induced tumor necrosis factor-a secretion, another inflammatory indicator. In addition, NaHS (10-300 lmol/L) dose-dependently decreased LPS-stimulated NO production in primary cultured astrocytes, suggesting that the anti-neuroinflammatory effect of H 2 S is not specific to microglial cells alone. Taken together, H 2 S produced an anti-inflammatory effect in LPS-stimulated microglia and astrocytes, which may be due to inhibition of inducible nitric oxide synthase and p38 MAPK signaling pathways. These findings may have important implications in the treatment of neuroinflammation-related diseases.

Exogenous hydrogen sulfide protects H9c2 cardiac cells against high glucose-induced injury by inhibiting the activities of the p38 MAPK and ERK1/2 pathways

“…Additionally, exogenous H 2 S reduces doxorubicin-induced cardiotoxicity by inhibiting the activation of the p38 MAPK pathway (29). Our results, as well as those from previous studies (22,29,40,41) suggest that exogenous H 2 S may be a potential inhibitor of p38 MAPK.…”

“…The involvement of hte inhibition of the p38 MAPK pathway in the cytoprotective effects of exogenous H 2 S has also been reported by other studies. Hu et al indicated that H 2 S suppresses LPS-induced inflammation by inhibiting p38 MAPK in microglia (40) and that H 2 S protects SH-SY5Y cells against rotenone-induced apoptosis through the suppression of p38 MAPK activation (41). Additionally, exogenous H 2 S reduces doxorubicin-induced cardiotoxicity by inhibiting the activation of the p38 MAPK pathway (29).…”

Flow cytometry for the assessment of animal sperm integrity and functionality: state of the art

“…71 Mitochondrial status Mitochondria, located in the sperm mid-piece generate a major part of the ATP required for sperm metabolism, membrane function and motility, alongside with anaerobic glycolysis in the cytoplasm. 19,[72][73][74] Besides, mitochondria are the coordinators of apoptosis mechanisms in a number of cell systems, 75,76 and they are involved in sperm maturation 72 and protection against damage induced by cryopreservation. 74 Recently mitochondrial proteins were found to be involved in the capacitation-dependent tyrosine phosphorylation in spermatozoa.…”

Gas Mediators in the Nervous System: Nitric Oxide, Hydrogen Sulfide and Carbon Monoxide

“…131 H 2 S glial hücrelerden NO ve TNF-α salınımını azaltarak, LPS ile oluşan inflamasyona karşı koruyucu etkili olduğu gösterilmiştir. 132 Farelerde H 2 S verilmesinin metabolik hızı ve vücut merkezi sıcaklığını azalttığı, yani "suspended" animasyon benzeri durum yaratabildiği gös-terilmiştir. Üstelik H 2 S verilmesi kesildiğinde hayvanın davranışsal ya da fiziksel bir değişiklik geçirmediği gözlenmiştir.…”